The primary functions of the rectum and anus are storage of feces and maintenance of bowel continence. The rectum is a capacitance organ. The wall of the rectum is highly elastic and distensible. This allows for storage of fecal material prior to the act of defecation. The anal canal is made up of mucosal lining cells that cover two muscular layers (the internal and external anal sphincters). These sphincters, particularly the external anal sphincter, function to hold back feces from exiting the rectum by remaining contracted until the appropriate time to defecate. A variety of inflammatory, ischemic infectious, traumatic and neoplastic disorders may affect the anorectal region. Symptoms of anorectal disease include anal or rectal pain, urgency to move the bowels, fecal incontinence, diarrhea, rectal bleeding, and difficulty with evacuation of the rectum.
Vitamin A has been demonstrated to accelerate wound healing following burn injury and surgeries in laboratory animals. The mechanism of this effect is not been fully elucidated, but increased crosslinking of collagen and myofibrils occur after vitamin A administration.
The present inventor recently described a dramatic case of the patient with AIDS and anal carcinoma with developed a large radiation-induced anal ulceration with marked debility. The patient required high dose opioid therapy for control of anal pain. After a twelve week course of orally administered vitamin A (in the form of retinol palmitate), the patient experienced complete wound healing and symptomatic relief that persisted for more than six months. Radiation proctopathy is a form of injury of the rectum from radiation therapy administered for pelvic cancers such as cancers of the prostate, uterus and ovary. The present inventor recently designed, conducted and published a randomized double-blinded trial comparing vitamin A in the form of retinol palmitate (10,000 IU by mouth for 90 days) to placebo in patients with radiation proctopathy. The present inventor has found that vitamin A significantly reduced rectal symptoms of radiation proctopathy, due perhaps to the wound healing effects of vitamin A. It is assumed that administration of vitamin A in a suppository form would have even greater efficacy for radiation proctopathy and other chronic conditions of the rectum, since the suppository allows for delivery of large concentrations of vitamin A directly at the affected area of the rectum and anus. The other form of vitamin A, (beta carotene), when applied topically, have the potential to enhance the effectiveness of retinol palmitate for treating radiation proctopathy and other anorectal disorders.
Suppositories are bodies of solid materials into which medications have been incorporated. These medications are then placed into body cavities. Medications are released at the site of placement, resulting in local effects of the medications.
Suppository forms of medications are available for placement in the anus and vagina for the treatment of anorectal and gynecologic disorders. The most common use of rectal suppositories is for the treatment of constipation. Rectal suppositories are also used as an alternative form of drug delivery in patients that cannot receive medications by mouth. Examples of these types of rectal suppositories include treatments for nausea and pain.
There are numerous anorectal diseases that may benefit from topically applied vitamin A and anti-oxidant agents. These conditions include (but are not limited to), inflammatory bowel disease (IBD) including ulcerative proctitis and Crohn's disease, anal fissures, internal hemorrhoids, radiation proctopathy, anal and rectal neoplasms, anal warts, anal dysplasia, solitary rectal ulcer syndrome, pruritis ani and anorectal ischemia. These conditions represent a variety of significant clinical problems for which limited treatment options are currently available.
Anorectal disorders are diagnosed by medical history, physical examination, endoscopic evaluation with flexible sigmoidoscopy or colonoscopy, anorectal ultrasound, CT scan and MRI of the pelvis. By far, the most commonly used and most important of these diagnostic modalities are the endoscopic evaluations.
Current treatment modalities for anorectal disorders depend on the condition treated. Except for treatments for IBD and anal fissures, most treatment modalities have not undergone rigorous scientific evaluation and are primarily empiric. A variety of oral medications are used for these conditions.
Topical treatments for IBD consist of the anti-inflammatory agent 5-aminosalicylic acid, as well as hydrocortisone, a steroid. Topical therapies for anal fissure consist of agents that relax the anal sphincter muscles including nitroglycerin and calcium channel blockers. Topical therapies for internal hemorrhoids include suppositories containing local anesthetics and/or hydrocortisone. Topical 5-ASA and sucralfate have been recommended for radiation proctopathy, but appear to be ineffective. Short chain fatty acid enemas have been used to treat radiation proctopathy but are not readily available and difficult to administer. Topical creams and local anaesthetics are used for pruritis ani, but no suppositories have been tried. No topical agents have been tested for solitary rectal ulcer syndrome, anorectal neoplasms or anorectal ischemia. Many patients with these conditions remain symptomatic despite treatment using the aforementioned medications.
Thus, there is a need to develop methods and compositions that may be used to treat chronic anorectal disorders. Ideally, identification of new agents that may also alter the pathophysiology of chronic anorectal disorders is suggested.